The 1-methyl-4-[(2,2-diphenyl-2-propoxy)acetoxy]piperidine hydrochloride (propiverine hydrochloride) is a non-selective peripheral anticholinergic agent having an affinity for the mAChR subtypes M1-M5. It is currently used to treat people who have urinary problems caused by an overactive bladder or by spinal cord injuries. It works by preventing spasms of the bladder muscle, thus being of help to reduce the episodes of urinary incontinence or reduce the feeling of urgency that bladder spasms can cause.
Propiverine hydrochloride is available in 15-mg tablets for immediate release to be administered twice per day or in 30-mg modified-release capsules to be administered once per day, such that the propiverine hydrochloride active ingredient is administered at the recommended daily dose of 30 mg in the above indications. However, an anticholinergic agent, such as propiverine, could be used for the treatment of a series of other disorders.
In chronic obstructive pulmonary disease (COPD) and asthma, cholinergic mechanisms contribute to increased bronchoconstriction and mucus secretion that limit airflow (Buels K S, Fryer A D. Handb Exp Pharmacol. 2012; 208, 317-41).
In cancers derived from epithelial and in endothelial cancer, the ability of muscarinic agonists to stimulate growth has been shown for melanoma, pancreatic, breast, ovarian, prostate and brain cancers, suggesting that M3 antagonists will also inhibit growth of these tumors (Spindel E R. Handb Exp Pharmacol. 2012; 208, 451-468).
The stratified epithelium enveloping the skin and lining the surfaces of oral and vaginal mucosa is comprised by keratinocytes that synthesize, secrete, degrade, and respond to ACh via muscarinic and nicotinic receptors express a unique combination of mAChR subtypes at each stage of their development. Drugs that block mAChRs, such as propiverine hydrochloride, have the potential of treating patients suffering from non-healing wounds, mucocutaneous cancers, and various autoimmune and inflammatory diseases. Successful therapy of pemphigus lesions with topical pilocarpine and disappearance of psoriatic lesions due to systemic atropine therapy illustrate that such a therapeutic approach is useful (Grando S. A. Handb Exp Pharmacol. 2012; 208, 429-450).
An anticholinergic agent having the properties of propiverine hydrochloride could also be useful in treating sialorrhea (Arbouw M. E. et al. Neurology. 2010 Apr. 13; 74/15, 1203-1207) and Ménière's disease.
Moreover, an anticholinergic agent having the properties of propiverine hydrochloride should antagonize the peripheral dose-limiting side effects of acetylcholine-esterase inhibitors (AChEIs), and thus enable the use of higher and therefore more effective doses of AChEIs in the treatment of Alzheimer-type dementia, post-surgical delirium, Mild Cognitive Impairment (MCI), and related central nervous system (CNS) hypocholinergic syndromes.